Peripheral neuropathies are conditions resulting from injury to the peripheral nervous system. Patients with these conditions experience weakness and sensory loss, for example, eyelid droop (ptosis) from loss of control of muscles, and muscle deterioration. The cause of the neuropathy in many patients is unknown, but in some cases it is associated with plasma cell dyscrasia, where individual clones of antibody-producing cells proliferate abnormally and produce antibodies (IgM) in excess. These antibodies are derived from the same clones and are thus monoclonal antibodies, designated as M-proteins. (McLeod et al (1984) Peripheral Neuropathy, p. 1847-1865, edited by Dyck et al, Saunders, Philadelphia; Latov (1984) in Neuroimmunology, p. 261-273, edited by Behan et al, Raven Press, N.Y.).
In some patients with neuropathy and plasma cell dyscrasia there are high concentrations of IgM M-proteins. The M-proteins have been shown to react with myelin and myelin-associated glycoproteins (MAG) to cause demyelination of the myelin sheath. (Braun et al., J. Neurochem. 39:1261-1265 (1982); Steck et al, Neurology 33:19-23 (1983); Ilyas et al, Proc. Nat'l Acad. Sci., U.S.A. 81:1225-1229 (1984)).
To date, the most successful treatment for peripheral neuropathies has been plasmapheresis wherein the patient's blood plasma is removed and replaced. Recent studies have indicated that the M-proteins bind to a carbohydrate determinant shared by a number of peripheral nerve glycoproteins, including MAG, and by two acidic glycolipids in peripheral nerves. (Chou et al, Biochem. Biophys. Res. Commun. 128:383-388 (1985); Chou et al, J. Biol. Chem. 261:11717-11725 (1986); Ariga et al, J. Biol. Chem. 262:848-853 (1987)). These investigators have reported that the reactive glycolipids are not gangliosides and that M-proteins directed against MAG probably bind to the same or closely related carbohydrate determinants. The glycolipid antigen was characterized as a sulfated glucuronic acid-containing paragloboside; a paragloboside is a lacto-N-neotetraosyl ceramide. [Schwarting et al. J. Immunol 118:1415-1419 (1977)]. Glucuronic acid-3-sulfates containing oligosaccharides have been found to be antigenic for M-proteins and have been used in characterization studies to isolate the IgM M-proteins. These naturally occurring oligosaccharides are generally pentasaccharide-containing ceramides which contain a terminal 3-sulfated glucuronic acid moiety. [Chou et al, J. Biol. Chem. 261:11717-11725 (1986); Ariga et al, J. Biol. Chem. 262:848-853 (1987)]. Such antigenic oligosaccharides are difficult and expensive to purify and/or synthesize. The present invention provides relatively inexpensive, synthetic monosaccharides that mimic the antigenic activity of naturally occurring products such as the M-protein antigens.